Humans are exposed to nitroheterocyclic compounds through extensive use in medicine and industry; these chemicals are metabolically 'activated' to toxic, DNA damaging and, in many cases, tumorigenic agents. We will attempt to determine the relationship between drug 'activation', DNA damage, mutagenicity and transforming ability of selected nitroheterocycles. Specifically, we will determine whether the electronegativity (reactivity of these chemicals) as reported in the literature, is correlated with their ability to damage DNA, as measured by hydroxylapatite chromatography, their mutagenicity in bacterial tester strains, or their ability to tranform cultured C3H/10T1/2 mammalian cells. In addition, we intend to determine whether the amount of nitrofuran-induced DNA damage or its rate of repair differs in specific target organs for tumor production, and further, whether this damage is due solely to metabolic activation in he target tissue or to tranfer of 'activated' intermediates of nitrofuran metabolism.